The objective of this research is to explore the effects of psychoactive drugs on brain cyclic nucleotide levels in vivo both prior to and following aggressive behavior. Nucleotides will be assayed from both whole brain and regional areas. This research will elicit additional information regarding drug-behavior interactions mediated through a changing, plastic, central nervous system. The emphasis on cyclic nucleotides is designed to supplement the study of the post-synaptic (and receptor) pharmacologic influences of aggression-altering drugs interacting with an animal's behavior. Such experimentation offers the potential for expanding our knowledge regarding the mechanisms of action of aggression-altering drugs and augmenting the predictability of the effects of new drugs on aggressive behavior. The proposal has several points of focus: 1) Our work will measure the effects of aggression-altering drugs (such as 6-hydroxydopamine, monoamine oxidase inhibitors, dibenzazepines, and rubidium) on baseline levels of brain cyclic nucleotides in whole brain and regional area. These drugs will be administered both acutely and subacutely. 2) We will explore the interactional effects of aggression-altering drugs with the changes in brain cyclic nucleotides which are correlated with aggressive behavior to examine whether these drugs facilitate or inhibit the nucleotide changes observed. 3) We will attempt to block and facilitate the nucleotide changes noted in parts 1 and 2 with receptor blockers and drugs altering cyclic nucleotides (such as methylxanthines) and observe whether the aggressive behavior is similarly altered. 4) Since drugs affect various types of aggressive behavior as well as dominant and submissive animals differentially, we shall conduct the experiments in parts 1, 2, and 3 by using different models of aggression and both dominant and submissive animals. 5) Lastly, as a final project within this proposal, we shall attempt to apply the drugs found effective in parts 1, 2, and 3 to specific regional areas of brain suggested by the regional alterations of cyclic nucleotides measured in the preceding experiments, in order to demonstrate site-specific pharmacological modulation of agonistic behavior with nucleotide-altering drugs.